The present invention relates to a method of chlorinating a side chain methyl group of 2-chloro-methylpyridine so as to produce 2-chloro-monochloromethylpyridine, 2-chloro-dichloromethylpyridine and/or 2-chloro-trichloromethylpyridine. These products are useful as raw materials of medicines such as anti-peptic ulcer and of insecticides.
In chlorination of a side chain methyl group of methylpyridine, hydrogen chloride produced by chlorination reacts with methylpyridine because nitrogen atom of pyridine nucleus functions as a base. With this, hydrochloride of methylpyridine is produced. As a side chain methyl group of methylpyridine is chlorinated to a higher order, electron attractivity of a side chain methyl group increases. With this, basicity of nitrogen atom decreases. Therefore, as compared with chlorinated methylpyridine, methylpyridine predominantly reacts with hydrogen chloride so as to produce hydrochloride of methylpyridine. This hydrochloride precipitates in the form of solid, and is very low in reactivity with chlorine. Therefore, it becomes difficult to successively chlorinate methylpyridine.
There are some proposals to prevent the formation of hydrochloride of methylpyridine. For example, as is disclosed in Angew. Chem. Internat. Edit., 144, 2 (1963) and German Patent 3,630,046, there is provided a method of chlorinating a side chain methyl group of methylpyridine in the presence of an inactive solvent and a hydrogen chloride acceptor such as sodium carbonate. JP-A-49-127977 discloses a method of chlorinating a side chain methyl group of methylpyridine in the presence of an inactive solvent, a hydrogen chloride acceptor and water.
However, if the above-mentioned methods are applied to chlorination of 2-chloro-methylpyridine which is represented by the following formula (1), chlorination will be stopped in the middle of the reaction due to the presence of water as an additive and/or water which is formed by neutralization of hydrogen chloride and a hydrogen chloride acceptor. ##STR1## In particular, in the case that water is added as an additive or as the reaction system is enlarged in size, chlorination is substantially inhibited. It is believed that a hydrogen chloride acceptor is dissolved in water and directly reacts with chlorine so as to prevent the formation of chlorine radical and thus to stop chlorination.
In the above conventional methods, a hydrogen chloride acceptor such as sodium carbonate in the form of solid is added. Therefore, the reaction liquid takes the form of slurry. Thus, it is necessary to add an inactive solvent such as carbon tetrachloride for adjusting the concentration of the slurry. However, the usage of a halogen-containing hydrocarbon such as carbon tetrachloride will be limited in the future from an environmental aspect and furthermore is not economical.